The Effect of Gemfibrozil, Ketoconazole and Clarithromycin on the Amount of LY2409021 in the Bloodstream

Phase 1

Completed

• Conditions: Healthy Volunteers
• Interventions: Drug: LY2409021; Drug: Gemfibrozil; Drug: Ketoconazole; Drug: Clarithromycin

• Registration Number: NCT01836198
• Lead Sponsor: Eli Lilly and Company

Brief Summary

The purpose of this study is to examine the effect of gemfibrozil, ketoconazole, and clarithromycin on how much LY2409021 is found in the bloodstream and how long the body takes to get rid of it. The study is split into two parts, Part A and Part B. Participants in Part A are divided into two cohorts (groups). Each cohort will participate in two study periods. Period 1 involves a single dose of LY2409021. Period 2 involves either gemfibrozil or ketoconazole given daily for 21 days with LY2409021 given once on Day 4. Part A will last for 51 days and will also involve screening within 27 days of the start of the study. Part B is only open to participants who successfully completed Part A of the study. Participants in Part B will receive clarithromycin given daily for 21 days with LY2409021 given once on Day 4. Part B will last for 29 days and will also involve screening within 27 days of the start of the study.

Detailed Description

Part B was added to the trial in August 2013, per protocol amendment.

Study Timeline

• Study First Submitted: 2013-04-16
• Study First Submitted QC: 2013-04-17
• Study First Posted: 2013-04-19
• Study Start: 2013-05
• Primary Completion: 2013-11
• Study Completion: 2013-11
• Results First Submitted: 2018-03-24
• Status Verified: 2018-11
• Results First Submitted QC: 2018-11-09
• Last Update Submitted: 2018-11-09
• Results First Posted: 2019-03-08
• Last Update Posted: 2019-03-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

• Participants are overtly healthy males or females, as determined by medical history and physical examination
• Participants have a body mass index (BMI) of 18.0 to 32.0 kilograms per meter squared (kg/m^2), inclusive, at screening
• Participants have a fasting blood glucose of 54 to 110 milligrams per deciliter (mg/dL) (3.0 to 6.1 micromoles per liter [mmol/L])

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Exclusion Criteria

• Participants that have a contraindication to use of clarithromycin
• Participants that have a personal or family history of long QT syndrome
• Participants with a family history of sudden unexplained death or cardiac death in an immediate family member under 60 years of age
• Participants with a personal history of unexplained syncope within the last year
• Participants who have taken drugs or substances known to be an inducer or inhibitor of cytochrome P450 (CYP)3A4 or CYP2C8 or CYP2J2 (for example, St. John's wort, rifampin, ketoconazole, trimethoprim) within 30 days prior to the first dose

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
LY2409021 Only (Part A, Cohort 2)	LY2409021	Part A, Period 1. Participants will receive a single 20-mg oral dose of LY2409021 on Day 1.
LY2409021+Ketoconazole (Part A, Cohort 2)	LY2409021	Part A, Period 2. Participants will receive a once-daily 400-mg oral dose of ketoconazole on Days 1-21 and a single 20-mg oral dose of LY2409021 on Day 4.
LY2409021+Clarithromycin (Part B)	LY2409021	Part B. Participants will receive a twice-daily 500-mg oral dose of clarithromycin on Days 1-21 and a single 20-mg oral dose of LY2409021 on Day 4.
LY2409021 Only (Part A, Cohort 1)	LY2409021	Part A, Period 1. Participants will receive a single 20-milligram (mg) oral dose of LY2409021 on Day 1.
LY2409021+Gemfibrozil (Part A, Cohort 1)	LY2409021	Part A, Period 2. Participants will receive a morning (AM) and evening (PM) oral dose of 600 mg gemfibrozil on Days 1-20 and an AM oral dose only of 600 mg gemfibrozil on Day 21. Participants will also receive a single 20-mg oral dose of LY2409021 on Day 4.
LY2409021+Gemfibrozil (Part A, Cohort 1)	Gemfibrozil	Part A, Period 2. Participants will receive a morning (AM) and evening (PM) oral dose of 600 mg gemfibrozil on Days 1-20 and an AM oral dose only of 600 mg gemfibrozil on Day 21. Participants will also receive a single 20-mg oral dose of LY2409021 on Day 4.
LY2409021+Ketoconazole (Part A, Cohort 2)	Ketoconazole	Part A, Period 2. Participants will receive a once-daily 400-mg oral dose of ketoconazole on Days 1-21 and a single 20-mg oral dose of LY2409021 on Day 4.
LY2409021+Clarithromycin (Part B)	Clarithromycin	Part B. Participants will receive a twice-daily 500-mg oral dose of clarithromycin on Days 1-21 and a single 20-mg oral dose of LY2409021 on Day 4.

Primary Outcome Measures

Name	Time	Method
Pharmacokinetics: Maximum Concentration (Cmax) of LY2409021	Predose and 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 144, 216, and 336 hours postdose (and 408, 504, and 576 hours postdose in Part A, Period 2 and Part B only)
Pharmacokinetics: Area Under the Concentration Curve From Zero to Infinity (AUC[0-∞]) of LY2409021	Predose and 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 144, 216, and 336 hours postdose (and 408, 504, and 576 hours postdose in Part A, Period 2 and Part B only)

Trial Locations

Locations (1)

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.; 🇺🇸 Evansville, Indiana, United States